Transcatheter valve for venous insufficiency

ABSTRACT

This application generally relates to an transcatheter anti-reflux venous valve endoprosthesis system, including a replacement valve, a valve support frame, crimping system, and delivery system to treat patients with chronic venous insufficiency, and method for using such a system.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims priority to and the benefit of ProvisionalApplication No. 63/340,867, filed on May 11, 2022 and ProvisionalApplication No. 63/404,150, filed on Sep. 6, 2022, the contents of whichare hereby incorporated by reference in their entireties.

FIELD

The present invention generally pertains to a transcatheter anti-refluxvenous valve endoprosthesis system, its methods of manufacture and itsuses.

BACKGROUND OF THE INVENTION

Chronic venous insufficiency (CVI) describes a condition that affectsthe venous system of the lower extremities with venous hypertensioncausing various pathologies including pain, swelling, edema, skinchanges, and ulcerations. It is characterized by failure of venousvalves to allow blood from the lower limbs to return to the heart,resulting in venous hypertension. Incompetence in venous valves createsreflux, which can lead to pain, itching, and severe and uncontrollableswelling that can reduce mobility and result in severe prolongedulcerations.

More serious consequences of CVI can include venous ulcers, which havean estimated prevalence of about 0.3%, although active or healed ulcersare seen in about 1% of the adult population. See Eberhardt R T,Raffetto J D. Chronic venous insufficiency. Circulation. (2005) May 10;111(18):2398-409. It has been estimated that about 2.5 million peoplehave severe cases of CVI in the United States, and of those, about 20%develop venous ulcers. The overall prognosis of venous ulcers is poor,with delayed healing and recurrent ulceration being common. More than50% of venous ulcers require prolonged therapy lasting more than a year.Individuals with CVI not only suffer the physical effects of thedisease, but also endure psychological ailments caused by undesiredcolor changes and bulging of the skin. In severe cases of CVI involvingdeep vein thrombosis and pulmonary embolism, death can occur.

The socioeconomic impact of venous ulceration also can be dramatic,resulting in an impaired ability to engage in social and occupationalactivities, thus reducing the quality of life and imposing financialconstraints. Disability related to venous ulcers often leads to loss ofproductive work hours, estimated at 2 million workdays/year, and maycause early retirement, which is found in up to 12.5% of workers withvenous ulcers DaSilva A, Navarro M F, Batalheiro J. “The importance ofchronic venous insufficiency: various preliminary data on itsmedico-social consequences.” Phlebologie. 1992; 45:439-43. The financialburden of venous ulcer disease on the healthcare system is readilyapparent: an estimated $1 billion is spent annually on the treatment ofchronic wounds in the United States, or up to 2% of the total healthcarebudget in all Western countries, and recent estimates place the cost ofvenous ulcer care at $3 billion annually. See Eberhardt supra.

Currently, the approved therapies for treatment of CVI are limitedmainly to compression garments, compression pumps, and wound dressings.See Raffetto J D. Dermal pathology, cellular biology, and inflammationin chronic venous disease. Thromb Res. (2009); 123 Suppl 4:S66-71.

In response to the need for improved treatments of patients sufferingfrom CVI, enVVeno Medical Corporation of Irvine, California developedthe VenoValve® system which offers a permanent, single-use implant forchronic venous insufficiency. The functional component of VenoValve® isa porcine aortic leaflet. VenoValve® is surgically implanted in the deepvein of the lower extremity by a licensed healthcare professional andsutured to the repaired vein. A description of the VenoValve®replacement valve is provided in U.S. Pat. No. 11,285,243 which ishereby incorporated by reference in its entirety.

A few other transcatheter valves have been disclosed which require useof multiple leaflets or stent or frame design to differentiate betweeninflow and outflow of blood when placed in the veins.

For example, Published U.S. Application No. 20170196692, which is herebyincorporated by reference in its entirety, describes an implantablevalve having a bulbous center section. The valve can supposedly beimplanted using a transcatheter delivery system, but the system requiresa capability to engage and release a valve with an enlarged bulboussection, which is wider than natural human vein.

Published U.S. Application No. 20190328511, which is hereby incorporatedby reference in its entirety, discloses a prosthetic transcatheter valvedevice with a distinct an anterograde end and a retrograde end. Theanterograde end of the device comprises a pair of leaflets opposinglypositioned with respect to one another.

Published U.S. Application 20090254175, which is hereby incorporated byreference in its entirety, discloses a meshed stent with lattices, whereboth its ends have spiral struts. The stent can house at least twoleaflets to create a one-way flow valve.

U.S. Pat. No. 7,744,642, which is hereby incorporated by reference inits entirety, describes a prosthetic transcatheter valve with a hollowbase disposed as an inflow end, a plurality of struts connected withthat base and extending to a blood outflow end; and inwardly orientedflanges disposed at the blood outflow ends of the struts. The valve hasleaflets in gaps between the struts and are supported by the frame.

Published U.S. Application 20180078372, which is hereby incorporated byreference in its entirety, discloses a radially expandable frame with aplurality of leaflets frame has a distinct inflow and outflow end. Theframe specifically requires a scalloped inflow and outflow edge as afunctional feature.

Published U.S. Application No. 20030055492A1, which is herebyincorporated by reference in its entirety, also discloses aself-expandable prosthetic transcatheter valve comprising more than twoleaflets and a wire frame with at least one zigzag section of the wire.

It has been observed that the ability to accurately guide and positionthe transcatheter valve for placement in a patient's deep venous systemis affected by factors such as the valve shape, valve size, targetposition, for example, where the device is to be moved through orpositioned across venous walls and/or at tortuous anatomy. There mayalso be issues with the coupling between the vein frame used for thevalve to be delivered, all of which can result in a less accurate, andtherefore less safe, device delivery process.

Given the prevalence and socioeconomic impact of CVI, an additional,alternative and effective treatment for CVI which is less surgicallyinvasive than current approaches and employs a monocusp valve isdesirable, particularly for patients who are candidates for thetranscatheter system described herein.

SUMMARY

The present invention provides a novel system design and delivery forthe treatment of chronic venous insufficiency.

A transcatheter valve system for implantation into a host vein of asubject is described. The transcatheter valve system can comprise avalve assembly.

In accordance with an exemplary embodiment, the valve assembly cancomprise at least one leaflet formed using a continuous biologicaltissue.

In one aspect of the embodiment, the at least one leaflet can be formedfrom a flat sheet of the continuous biological tissue that is foldedform a monocusp shape. In an exemplary embodiment, the exact geometry isnot being replicated, but the function of the native valve is achievedby opening and closing under physiologically relevant pressure gradientscausing the vortex operation with respect to blood flow using a monocuspleaflet that allows the leaflet to open and to smoothly and quicklyclose. The at least one leaflet's cusp can be folded from a continuousbiological tissue, and thus suturing is not required to form the apex ofthe leaflet's cusp. However, suturing can be used to form the margins ofthe leaflet's cusp.

In an exemplary aspect, the biological tissue can be from a xenogeneicsource.

In one aspect, the xenogeneic source is selected from the groupconsisting of porcine, bovine, and equine. In a preferred aspect, thexenogeneic source is porcine. In another aspect, the xenogeneic sourceis xenogeneic pericardium. In another aspect, the xenogeneic source isporcine pericardium.

In one aspect, the valve assembly can comprise exactly one leaflet. Inone aspect of the exemplary embodiment, the leaflet's cusp is furtherformed by cutting the continuous biological tissue to a shape having atop section resembling the shape of a cusp and a bottom section (wall)that is generally rectangular in shape; folding the top section over thebottom rectangular section such that the apex of the leaflet's monocuspis created; and suturing the top section onto the bottom rectangularsection of the biological tissue to form margins of the monocusp. In oneaspect, an inflow skirt (inflow conduit) is attached to the wall (e.g.,the rectangular shaped bottom section), which provides a way to avoidflow disruption on the inflow side of the device.

In a further aspect, the inflow skirt is attached to the wall andleaflet. In some specific aspects, the inflow skirt material can be madeusing a biological tissue from a xenogeneic source. The xenogeneicsource can be selected from the group consisting of porcine, bovine, andequine. In one aspect, the xenogeneic source is porcine. In anotheraspect, the xenogeneic source is pericardium. In another aspect, thexenogeneic source is a porcine pericardium. In one aspect, the inflowskirt material has the same source as the monocusp leaflet. In yetanother aspect, the inflow skirt material has a shape that isapproximately rectangular. In a further aspect, the inflow skirtmaterial has a generally square shape.

In more specific aspects, the biological tissue is fixed/crosslinked forcertain period of time in a fixative. In a further aspect, the fixativeis a solution that includes glutaraldehyde, formaldehyde, osmiumtetroxide, genipin, hexamethylene diisocyanate (HMDI), a chemical or anaturally occurring fixative. In one aspect, the fixative isglutaraldehyde. In another aspect the fixative is 0.2% buffered isotonicglutaraldehyde.

In some aspects, the biological tissue is treated with a solution toreduce bioburden levels post fixation. In more specific aspects, thebioburden reduction solution is a mixture of Isopropyl Alcohol (IPA) andbuffered isotonic glutaraldehyde. In a specific aspect, the bioburdenreduction solution has about 1% to 80% IPA included in the solutionmixture. In one aspect, the bioburden reduction solution has about 20%IPA included in the solution mixture.

In some other aspects, the biological tissue and the inflow skirt areattached to another skirt, which is located on the circumference. Insome specific aspects, the skirt material can be made using a fabricskirt. Such fabric can include PET, PTFE fabric, ePTFE, degradablescaffold, collagen scaffold, hyaluronic acid scaffold, fibrin, a polymerbased degradable or non-degradable material, or a biologic material. Inone specific embodiment, the material has ultra-low profile, adequateporosity and suture retention, surface roughness, scaffold for cellattachment, and surface area able to attract migrated native cells topromote tissue ingrowth for improved device sealing and long-term devicemigration resistance post-implantation.

In yet another aspect, the skirt material has a shape that isapproximately rectangular. In a further aspect, the skirt material has agenerally rectangular shape with slightly wider sections (flared) atinflow and/or outflow. In some specific aspects, the skirt material hasa shape that matches the shape of the wall and inflow skirt whenattached together.

In one aspect, the at least one leaflet is attached to a frame. Inanother aspect, the at least one leaflet is attached to the frame usingsutures. The at least one leaflet can be attached to the frame such thatit partially covers the circumference of the frame. In another aspect,the at least one leaflet is attached to the frame such that it fullycovers the circumference of the frame.

In one exemplary aspect, the at least one leaflet attached to an inflowskirt material is attached to a frame. In one aspect, the at least oneleaflet attached with the inflow skirt material is attached to the frameusing sutures.

In one exemplary embodiment, the sutures are a polybutester monofilamentsuture used to attach the inflow skirt material, the wall, and leafletto the frame. In one aspect, the at least one leaflet attached with theinflow skirt material is attached to the frame, wherein the at least oneleaflet attached with the inflow skirt material is attached to the framepartially covers the circumference of the frame. In another aspect, theat least one leaflet attached with the inflow skirt material is attachedto the frame, wherein the at least one leaflet attached with the inflowskirt material is attached to the frame fully covers the circumferenceof the frame. In another aspect, the at least one leaflet attached withthe inflow skirt material is attached to the frame using sutures.

In any of these exemplary aspects, the leaflet may be covered with afabric skirt before suturing it into a frame. Also, in any of theseexemplary aspects, the at least one leaflet attached to an inflow skirtmaterial may be covered with a fabric skirt before suturing it to aframe.

In one exemplary embodiment, the at least one leaflet attached with theinflow skirt material when folded into a cylinder and attached to thecircumferential fabric skirt attached to the frame, has an outerdiameter of about 6 to about 18 mm. In one aspect, the at least oneleaflet attached with the skirt material when folded into a cylinder andattached to the circumferential fabric skirt attached to the frame, hasan outer diameter of about 9 mm to about 12 mm. The circumferentialfabric skirt material helps prevent migration and aids in sealing thatprevents flow circulation around valve.

In accordance with yet another exemplary embodiment, a method ofmanufacturing a replacement transcatheter valve for a subject isdescribed. The method comprises providing a continuous biological tissuesubjected to a fixation treatment; cutting the fixated biological tissuein a specific shape to have a top section and a bottom section; foldingthe top section onto the bottom such that an apex of a monocusp of aleaflet is created; and suturing the top folded section onto the bottomfolded section along the margins to form the monocusp shape of theleaflet. The method can further comprise attaching the monocusp leafletonto a tissue (inflow) skirt with sutures. The method can furthercomprise attaching the monocusp leaflet sutured to the tissue inflowskirt onto a fabric skirt.

In one aspect of the embodiment, the top section can resemble a shape ofa native cusp. In another aspect, the bottom section is approximatelyrectangular in shape.

In one aspect, the specific shape of the cut biological tissue is asrepresented in FIG. 3A.

In one aspect, the continuous biological tissue can be from a xenogeneicsource.

In another aspect, the xenogeneic source is selected from the groupconsisting of porcine, bovine, and equine. In one aspect, the xenogeneicsource is porcine. In another aspect, the xenogeneic source ispericardium. In yet another aspect, the xenogeneic source is porcinepericardium.

In an exemplary embodiment, the exact geometry is not being replicated,but the function of the native valve is achieved by opening and closingunder physiologically relevant pressure gradients causing the vortexoperation with respect to blood flow using a monocusp leaflet thatallows the leaflet to open and to smoothly and quickly close. The atleast one leaflet's cusp can be folded from a continuous biologicaltissue, and thus suturing is not required to form the apex of theleaflet's cusp. However, suturing can be used to form the margins of theleaflet's cusp. In one aspect, the monocusp shape replicates thespherical geometry of a native valve with an apex and margins to providea spatial buffer between the monocusp and the valve wall when the valveis in the open position, preventing or reducing adherence of themonocusp to the valve wall and facilitating closing of the monocuspvalve when adequate flow pressure gradient is created.

In a further aspect, inflow skirt material can be attached to the walland made using a biological tissue from a xenogeneic source. Thexenogeneic source can be selected from the group consisting of porcine,bovine, and equine. In one aspect, the xenogeneic source is porcine. Inanother aspect, the xenogeneic source is a pericardium. In anotheraspect, the xenogeneic source is a porcine pericardium. In yet anotheraspect, the inflow skirt material has the same source as the monocuspleaflet.

In one exemplary embodiment, the method of manufacturing comprisesattaching the leaflet to a frame. In one aspect, the method comprisesattaching the leaflet to the frame using sutures. In another aspect, themethod comprises attaching the leaflet to the frame such that itpartially covers the circumference of the frame. In another aspect, themethod comprises attaching the leaflet to the frame such that it fullycovers the circumference of the frame.

In one exemplary embodiment, the method of manufacturing comprisesattaching the leaflet attached to the inflow skirt material to a frame.In one aspect, the method comprises attaching the leaflet attached tothe inflow skirt material to the frame using sutures. In another aspect,the method comprises attaching the leaflet attached to the inflow skirtmaterial to the frame such that it partially covers the circumference ofthe frame. In another aspect, the method comprises attaching the leafletattached to the inflow skirt material to the frame such that it fullycovers the circumference of the frame.

In any of these aspects, the method of manufacturing can compriseattaching the leaflet to a fabric skirt before suturing it to a frame.Also in any of these aspects, the method of manufacturing can compriseattaching the leaflet attached to an inflow skirt material to a fabricskirt before suturing it to a frame. In one aspect, the fabric skirt canbe natural or synthetic. In another aspect, the fabric is polyethyleneterephthalate (PET). In yet another aspect, the fabric is such that thematerial has ultra-low profile, adequate porosity and suture retention,surface roughness, scaffold for cell attachment, and surface area ableto attract migrated native cells to promote tissue ingrowth for improveddevice sealing and long-term device migration resistancepost-implantation.

In accordance with an exemplary embodiment, the valve assembly cancomprise an implantable vein frame. The design of the vein framedescribed herein addresses deployment issues in part due to the framebeing compressible and expandable such as self-expanding with cellulargeometry, structures and holes for holding sutures, as well as strutmembers, cells, and crowns (with or without anchors) employed on thesurface of the frame.

In one exemplary embodiment, the implantable frame has anchors or hooksat the distal end of the flared cylinder to help prevent migration uponimplantation. In some aspects, the anchors or hooks help aid theattachment of the vein frame, before the PET skirt has encouraged celland tissue growth into the device. In some aspects, the anchors or hooksprevent traveling of the frame soon after insertion. In another aspect,the anchors or hooks may be located along the cylinder and are capableof grasping and/or anchoring into the native vein. The anchor or hooksmay also be located at certain sections along the cylinder, such as themedial sections. The anchors or hooks along the cylinder may also takethe form of individual tines. The anchors or hooks may be configuredwith different sizes based on the native vein.

In one exemplary embodiment, the implantable frame can comprise a firstsection, a second section, a third section, and a fourth section suchthat each section is interconnected to at least one other section. Insome aspects, the first section is interconnected to the second section,the second section is interconnected to the third section and the firstsection, the third section is interconnected to the second section andthe fourth section, and the fourth section is interconnected to thethird section. In some aspects, the sections are interconnected with astrut member.

In some exemplary embodiment, each section can comprise about two tosixteen zigzag segments with two to sixteen proximal peaks and about twoto sixteen distal peaks. In a preferred aspect, each section cancomprise about twelve zigzag segments with about twelve proximal peaksand about twelve distal peaks. The design of the frame provides radialstrength and is compressible. In some aspects, the sections areinterconnected by connecting every alternating proximal peak of onesection with alternating distal peak of the other section. In suchaspects, there can be about six strut members between two sections. Insome other aspects, the sections can be interconnected by connectingevery third alternating proximal peak of one section with every thirdalternating distal peak of the other section. In such aspects, there canbe about four strut members between two sections. In yet other aspects,the sections can be interconnected by every fourth alternating proximalpeak of one section with every fourth alternating distal peak of theother section. In such aspects, there can be three strut members betweentwo sections. In one aspect, the sections are rigidly interconnectedusing the strut members, which increases stability during valveplacement while balancing enough flexibility during valve function andrigidity in the vein.

In some aspects, the implantable frame can have suture holes on one orboth ends that can aid to attach the implantable frame to a valveassembly. In some specific aspects, the implantable frame has sutureholes on both ends of the frame. In another embodiment, the suture holesare at the crowns of the frame zigzags. In another specific aspect, thesuture holes have a diameter of about 0.5 mm, which allows framedurability and stress distribution optimization. In some aspects, thesuturing holes can be about 0.3 mm to about 1.0 mm in diameter. Thesutures can be stitched around each strut of the frame about threetimes. In another aspect, the sutures are stitched around each strut ofthe frame from about one to about five times. In another embodiment, thesuture holes are at the crowns of the frame zigzags, where the crown canalso be configured with anchors to reduce the potential for migration.In another aspect, anchors or hooks may be located along the cylinderand are capable of grasping and/or anchoring into the native vein. Theanchor or hooks may also be located at certain sections along thecylinder, such as the medial sections. The anchors or hooks along thecylinder may also take the form of individual tines. The anchors orhooks may be configured with different sizes based on the native vein.

In some aspects, the implantable frame has flared ends. For example, oneend of the implantable frame can have an outer diameter of D1 and theother end can have an outer diameter of D2. In some aspects, D1 and D2are substantially different. In some other specific aspects, D1 and D2are substantially similar. In some specific aspects, D1 and D2 can rangefrom about 6 mm to about 18 mm, about 10.8 mm to about 14.4 mm.

In some aspects, the diameter of the implantable frame between the firstsection and the second section can have a diameter of D3. In somespecific aspects, D3 can range from about 6 mm to about 18 mm, about 9mm to about 12 mm. In some other aspects, D1 can be about 1 mm to about3 mm larger than D3. A benefit of the size of the frame variations is tocater to different size veins and patient needs and to provide propervein anchorage and to reduce the potential for migration.

In some aspects, the diameter of the implantable frame between thesecond section and the third section can have a diameter of D4. In somespecific aspects, D4 can range from about 6 mm to about 18 mm, about 9mm to about 12 mm. In some other specific aspects, D1 can be about 1 toabout 3 mm larger than D4.

In some aspects, the diameter of the implantable frame between the thirdsection and the fourth section can have a diameter of D5. In somespecific aspects, D5 can range from about 6 mm to about 18 mm, about 9mm to about 12 mm. In some other specific aspects, D1 can be about 1 toabout 3 mm larger than D5. In some specific aspects, D3 and D5 aresubstantially different. In some other specific aspects, D3 and D5 aresubstantially similar.

In one exemplary embodiment, the implantable frame can be flared at oneend of the frame. In some aspects, the outer diameter of the flared endcan be less than about 18 mm. In preferred aspects, the outer diameterof the flared end can be about 10.8 mm to about 14.4 mm.

In another exemplary embodiment, the implantable frame can be flared atboth ends of the frame. In some aspects, the outer diameter of theflared ends can be less than about 18 mm. In preferred aspects, theouter diameter of the flared ends can be about 10.8 mm to about 14.4 mm.

In some aspects, the zigzag segments in the implantable frame createscells. In some aspects, the number of cells in the implantable frame isless than or equal to about 32. In some aspects, the number of cells inthe implantable frame is about 24. In some aspects, the number of cellspresent in the implantable frame provide sufficient radial strength ofabout 2-60 N, and to a range of about 17-20 N.

In some aspects, the size of the strut members between two specificsections can be different. For example, the size of strut membersbetween the first section and the second section and the size of strutmembers between the third section and the second section can bedifferent.

In some aspects, the size of the strut members between two specificsections can be significantly similar. For example, the size of strutmembers between the first section and the second section and the size ofstrut members between the third section and the second section can bethe same.

In one exemplary embodiment, the implantable frame is self-expandingonce crimped. In one embodiment, the frame is crimpable with a radialstrength of about 17-20 N. In some aspects, the implantable framecomprises a material capable of significant recoverable strain to assumea low profile for delivery or implantation. After release of thecompressed self-expanding frame, it is preferred that the implantableframe be capable of radially expanding back to its original diameter orclose to its original diameter. In some aspects, the implantable frameis made from material with high elastic strain (such as super elastic)to undergo large deformations and immediately return to its undeformedshape, and is heat treated.

Particularly preferred materials for self-expanding implantable framesinclude shape memory alloys that exhibit superelastic behavior (e.g.,are capable of significant distortion without plastic deformation).Frames manufactured of such materials may be significantly compressedwithout permanent plastic deformation, for example so that that can becompressed such that the maximum strain level in the stent or frame isbelow the recoverable strain limit of the material. Discussions relatingto nickel titanium alloys and other alloys that exhibit behaviorssuitable for frames can be found in, for example, U.S. Pat. No.5,597,378 (Jervis), which is hereby incorporated by reference in itsentirety, and International Application WO 95/31945 (Burmeister et al.),which is hereby incorporated by reference in its entirety. A preferredshape memory alloy is Ni—Ti, although any of the other known shapememory alloys may be used as well. Such other alloys include: Au—Cd,Cu—Zn, In—Ti, Cu—Zn—Al, Ti— Nb, Au—Cu—Zn, Cu—Zn—Sn, CuZn—Si, Cu—Al—Ni,Ag—Cd, Cu—Sn, Cu—Zn—Ga, Ni—Al, Fe—Pt, U—Nb, Ti—Pd—Ni, Fe—Mn—Si, and thelike. One suitable material possessing desirable characteristics forself-expansion is Nitinol, a Nickel-Titanium alloy that can recoverelastic deformations of up to 10 percent. This unusually large elasticrange is commonly known as superelasticity.

In one exemplary embodiment, the implantable frame is capable of beingexpanded by use of a balloon. Such a frame may not be self-expanding. Insome aspects, the implantable frame may be manufactured from an inert,biocompatible material with high corrosion resistance that can beplastically deformed at low moderate stress levels, such as tantalum.The implantable frames can be deployed by both assisted (mechanical)expansion (e.g., balloon expansion, and self-expansion means). In someaspects, the implantable frame can be made from materials that can beplastically deformed through the expansion of a mechanical assistdevice. When the balloon is deflated, the implantable frame can remainsubstantially in the expanded shape. Other acceptable materials includestainless steel, cobalt chromium, titanium ASTM F63-83 Grade 1, niobiumor high carat gold K 19-22. One widely used material for balloonexpandable structures is stainless steel, particularly 316 L stainlesssteel. Alternative materials for mechanically expandable structuralframes that maintain similar characteristics to stainless steel includetantalum, platinum alloys, niobium alloys, and cobalt alloys.

In one exemplary embodiment, an implantable frame can also be coatedwith or formed from one or more degradable synthetic materials (e.g.,polymers) and/or naturally derived materials (e.g., biologicalmaterials), as well as copolymers of degradable polymers and/orbiological materials. A bioactive material can be mixed with orcopolymerized with the bioabsorbable polymer or biological material.Alternatively, the bioactive material or a mixture of bioactive materialand biostable or bioabsorbable polymer or biological material can becoated with a second layer comprising a bioabsorbable polymer orbiological materials.

Bioabsorbable polymers or biological materials can be formed bycopolymerization of compatible monomers or by linking orcopolymerization of functionalized chains with other functionalizedchains or with monomers. Examples include crosslinkedphosphorylcholine-vinylalkylether copolymer and PC-Batimastatcopolymers, collagen, chitosan, hyaluronic acid, and fibrin. In oneaspect, the implantable frame can be coated with a coating of betweenabout 1 μm and about 50 μm, or between about 3 μm and about 30 μm,although any suitable thickness can be selected.

In some aspects, upon implantation, absorption of the bioabsorbablepolymer or biological materials can release a bioactive. Bioabsorbablepolymers or biological materials can be formed by copolymerization ofcompatible monomers or by linking or copolymerization of functionalizedchains with other functionalized chains or with monomers. Examplesinclude crosslinked phosphorylcholine-vinylalkylether copolymer andPC-Batimastat copolymers, collagen, chitosan, hyaluronic acid, andfibrin. In some aspects, the implantable frame can be coated with acoating of between about 1 μm and about 50 μm, or between about 3 μm andabout 30 μm, although any suitable thickness can be selected. Thecoating can comprise a bioactive material layer contacting a separatelayer comprising a carrier, a bioactive material mixed with one or morecarriers, or any combination thereof. The carrier can be biologically orchemically passive or active but is selected and configured to provide adesired rate of release of the bioactive material. In some aspects, uponimplantation, absorption of the bioabsorbable polymer or biologicalmaterial does not release a bioactive. In some aspects, the implantableframe can tissue engineered (bio-engineered).

In another exemplary embodiment, the implantable frame is made ofnon-degradable materials. Some examples of non-degradable materialsinclude polymers, metals, and biological materials. Such materials forimplantable frame include those materials that can provide the desiredfunctional characteristics with respect to mechanical load bearing,biological compatibility, modulus of elasticity, radio-opacity, or otherdesired properties. For some exemplary embodiments, the materials usedto form the implantable frames can comprise a material that exhibitsexcellent corrosion resistance.

In some aspects, the material can be selected to be sufficientlyradiopaque and create minimal artifacts during magnetic resonanceimaging techniques (MRI). In some aspects, the implantable frame cancomprise a metal, a metal alloy, a synthetic material, a naturallyderived material, or any suitable combination thereof, for example asframe with multiple layers. In some aspects, the implantable frame cancomprise nitinol, titanium, cobalt chromium, or PEEK. In a preferredaspect, the implantable frame is made of nitinol.

In one exemplary embodiment, the implantable frame may receive surfacemodification such as, but not limited to, electropolishing, passivation,anti-thrombogenic coating, coating with proper cell receptor bindingsites embedded on the surface or in a biological or polymeric coating,coating that promotes tissue ingrowth, or a combination thereof.

In one exemplary embodiment, the implantable frame can allow radialcompression of the implantable frame (e.g., crimping) resulting in a lowprofile to be used with a catheter delivery system. In some aspects, thecrimpability of the implantable frame is about 6 Fr to about 20 Fr. In apreferred aspect, the crimpability of the implantable frame is about 12Fr to about 16 Fr.

In one exemplary embodiment, the implantable frame can be fabricatedusing any suitable method known in the art. In some aspects, thecomplete frame structure is cut from a solid tube or sheet of material,and thus the implantable frame would be considered a monolithic unit.Laser cutting, water-jet cutting and photochemical etching are allmethods that can be employed to form the structural frame from sheet andtube stock. Still other methods for fabricating and/or shape setting thecomplete frame structure as previously disclosed would be understood byone of skill in the art. Techniques for forming implantable frames arediscussed, for example, in Dougal et al., “Stent Design: Implicationsfor Restenosis.” Rev. Cardiovasc Med. 3 (suppl. 5), S16-S22 (2002),which is incorporated herein by reference in its entirety.

In some embodiments, connections between the sections and zigzagsegments may be by welding or other suitable connecting means. Otherconnection means include the use of a binder, heat, or chemical bond,and/or attachment by mechanical means, such as pressing, welding orsuturing. In some aspects, portions of the implantable frame may beattached by applying a bonding coating. In a preferred aspect, theimplantable frame is made by laser-cutting from raw tubing material ofNitinol with following dimensions: less than about 18 mm outer diameter,such as about 4 mm outer diameter, with thickness of less than about 1mm, such as about 0.52 mm wall thickness.

In one exemplary embodiment, an implantable frame can optionally besterilized using any suitable technique known in the art, or equivalentsthereto. For example, an implantable frame can be sterilized using gammaradiation, ethylene oxide, solution, or electron beam sterilization withpreference on gamma radiation. In some embodiments, a sterilizedimplantable frame satisfies a minimum Sterility Assurance Level (SAL) ofabout 10⁻⁶.

In one exemplary embodiment, the implantable frame or portion thereofcan optionally comprise material that permits identification of theposition or orientation of the implantable frame within a body passage.In some aspects, portions of the implantable frame can include aradiopaque material that can be identified by X-rays. In some aspects,the implantable frame can also comprise materials that are useful withcontrast dyes to identify the implantable frame within a body passage.Non-limiting examples of radiopaque materials include, but are notlimited to, high-density metals such as platinum, iridium, gold, silver,tantalum or their alloys, or radiopaque polymeric compounds. Radiopaquematerials are highly visible under fluoroscopic illumination and arevisible even at minimal thickness. In some aspects, the radiopaquematerial can be gold, platinum, tungsten, or iridium, as well asmixtures and alloys thereof, in an eyelet structure attached to one ormore bridging member.

According to the aspects of the exemplary embodiment for the implantableframe, it may be seen variations may exist. It is further contemplatedthat other configurations of the implantable frame may exist, includingfor example variations having a fifth section.

The transcatheter system can comprise one or more aspects of atranscatheter valve and the implantable frame described above.

In one exemplary embodiment, a method comprising providing atranscatheter valve system for implantation into a host vein of asubject suffering from chronic venous insufficiency is disclosed.

In one aspect of the embodiment, the leaflet is formed from a sheet ofthe continuous biological tissue that is folded into a monocusp shape.The monocusp shape may replicate the spherical geometry of a nativevalve with an apex and margins. In an exemplary embodiment, the exactgeometry is not being replicated, but the function of the native valveis achieved by opening and closing under physiologically relevantpressure gradients causing the vortex operation with respect to bloodflow using a monocusp leaflet that allows the leaflet to open and tosmoothly and quickly close. The at least one leaflet's cusp can befolded from a continuous biological tissue, and thus suturing is notrequired to form the apex of the leaflet's cusp. However, suturing canbe used to form the margins of the leaflet's cusp. In another specificaspect, the suture holes have a diameter of about 0.5 mm, which allowsdurability and stress distribution optimization. In one exemplaryaspect, the suture holes are spaced about 1.5 mm apart. In otheraspects, suture holes can be spaced about 0.5 mm to about 3 mm apartfrom one another.

In another aspect, the suturing spacing reduces leakage with overlap ofsutures. In one aspect, the monocusp shape replicates the sphericalgeometry of a native valve with an apex and margins to provide a spatialbuffer between the monocusp and the valve wall when the valve is in theopen position, preventing or reducing adherence of the monocusp to thevalve wall and facilitating closing of the monocusp valve when adequateflow pressure gradient is created. The leaflet's cusp does not requiresuturing to form the apex of the leaflet's cusp. However, suturing canbe used to form the margins of the leaflet's cusp. In one aspect, theleaflet's cusp is further formed by cutting the continuous biologicaltissue to a shape with a top section resembling the shape of a cusp andbottom rectangular section; folding the top section over the bottomrectangular section such the apex of the leaflet's monocusp is created;and suturing the top section to the bottom rectangular section of thebiological tissue to form margins of the monocusp.

In accordance with another exemplary embodiment, a transcatheterdelivery device is provided. The present invention effectively providesa delivery system wherein the delivery device can be manipulated andguided to implant a transcatheter valve into a vein. The delivery deviceincludes, for example, an inner tube assembly, a sheath assembly, acatheter assembly, and a handle.

The inner tube assembly can include a flush port and a hypotube.

The sheath assembly includes nose cone and a nose cone-braided shaft. Inone aspect, the sheath assembly is connected to the inner tube assemblyby having the hypotube of the inner tube assembly cover the nosecone-braided shaft of the sheath assembly partially or completely. Thecatheter assembly is configured to contain the transcatheter valve in acompressed arrangement. The catheter assembly can be slidably placedover the sheath assembly, and includes a proximal region and a distalregion. In one aspect, one end of the proximal region of the catheterassembly is connected to the handle and the other end of the proximalregion of the catheter assembly is connected to the distal region of thecatheter assembly.

In another aspect, one end of the distal region of the catheter assemblyis configured to compressively contain the transcatheter valve in acompressed arrangement and the other end of the distal region of thecatheter assembly is connected to the proximal region of the catheterassembly. The distal region of the catheter assembly can be configuredto compressively contain the transcatheter valve has two shapes. Thefirst shape has a first diameter and the second shape has a seconddiameter. Both the shapes can be contiguous in nature or assembled.

The handle is configured to selectively move the catheter assemblyrelative to the sheath assembly. The delivery device can be configuredto provide a resting state in which the distal region of the catheterassembly is closer to the nose cone and a delivery state in which thedistal region of the catheter assembly is pulled away from the nosecone. The distal section of catheter is pulled back by turning the knobon the handle, causing the valve to be exposed; therefore, the handlecauses the distal section of catheter to slide back over the nose conesheath.

In one exemplary embodiment, the delivery device includes an indicatorfor when the self-expanding valve can no longer be repositioned. Theindicator aids the placement and timing of delivery of the valve, as itis clear how far the valve extrudes from the delivery device. A furtherembodiment of the indicator can indicate when approximately 20% of valvedeployment that the valve can no longer be retracted into the deliverydevice.

In a preferred exemplary embodiment, the delivery system provides threefunctions in one, as the device acts as a dilator, introducer sheath,and delivery system. In this embodiment, the three in one system allowsfor the device to not separately need a dilator or introducer sheath, asthe tapered bullet shape nose cone provides atraumatic entry acting as adilator and the distal region of catheter assembly has a continuous anduniform diameter acting as an introducer sheath.

The disclosure also provides an improved method of treating chronicvenous insufficiency (CVI) over conventional methods which manage CVI bydeactivation of incompetent veins through chemical or mechanicalblockage. The transcatheter valve described herein prevents blood refluxwithout permanently deactivating the damaged veins, thus providing animproved method for treating CVI by replacing and restoring functions ofincompetent valves to maintain proper blood flow.

The disclosure also provides a system for treating CVI in patients. Thesystem includes a transcatheter device and the delivery device asdescribed above. The transcatheter device includes an implantable frameand a transcatheter valve attached to the frame. Upon assembly of thesystem to a resting condition, the catheter assembly in the deliverydevice compressively contains the transcatheter device in the compressedarrangement over the sheath assembly. The system can be transitioned toa delivery state in which the distal region of the catheter assembly ispulled away from the nose cone such that it exposes the transcatheterdevice over the nose cone for release from the delivery device.

The disclosure also provides a method for treating chronic venousinsufficiency in patients. The method includes receiving a transcatheterdevice including an implantable frame and a transcatheter valve attachedto the frame. The delivery device includes an inner tube assembly, asheath assembly, a catheter assembly, and a handle. The inner tubeassembly includes a flush port and a hypotube. The sheath assemblyincludes nose cone and a nose cone-braided shaft. In one aspect, thesheath assembly is connected to the inner tube assembly by having thehypotube of the inner tube assembly cover the nose cone-braided shaft ofthe sheath assembly partially or completely. The catheter assembly isconfigured to contain the transcatheter valve in a compressedarrangement. The catheter assembly is slidably placed over the sheathassembly, and includes a proximal region and a distal region. In oneaspect, one end of the proximal region of the catheter assembly isconnected to the handle and the other end of the proximal region of thecatheter assembly is connected to the distal region of the catheterassembly.

One end of the distal region of the catheter assembly can be configuredto compressively contain the transcatheter valve in a compressedarrangement and the other end of the distal region of the catheterassembly is connected to the proximal region of the catheter assembly.In one aspect, the distal region of the catheter assembly configured tocompressively contain the transcatheter valve can have two shapes. Thefirst shape has a first diameter and the second shape has a seconddiameter. Both the shapes can be contiguous in nature or assembled. Thehandle is configured to selectively move the catheter assembly relativeto the sheath assembly. The delivery device is configured to provide aresting state in which the distal region of the catheter assembly iscloser to the nose cone and a delivery state in which the distal regionof the catheter assembly is pulled away from the nose cone. In someaspects, the method comprises having the delivery device such that thecatheter assembly in the delivery device compressively contains thetranscatheter device in the compressed arrangement over the sheathassembly.

The transcatheter valve can comprise biological tissue from a xenogeneicsource. The biological tissue can comprise at least one leaflet from axenogeneic source such as porcine, bovine, and equine. In some aspects,the at least one leaflet of the transcatheter valve is attached to aninflow skirt material, as described above. The method further comprisesproviding a frame to which is attached through the fabric skirt of thetranscatheter valve. The transcatheter valve can be attached to theframe such that it partially or fully covers the circumference of theframe. In a specific aspect, the at least one leaflet attached with theskirt material is attached to the frame using sutures.

In one aspect, the method further comprises creating a fenestration inthe host vein, the fenestration having a shape generally correspondingto the patch. In the preceding aspect, the fenestration may be createdgenerally on the external iliac vein, iliac vein, femoral vein, commonfemoral vein, popliteal vein, superficial vein system, great saphenousvein, profunda vein, or the external jugular vein. The method mayfurther comprise attaching the transcatheter valve to the host vein atthe fenestration. In a still further aspect, the transcatheter have beensubjected to a fixation treatment. In any of these aspects, the subjectmay be human.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1A is a longitudinal view of a venous valve with a fabric skirtcovered frame, inflow skirt, and leaflet according to an exemplaryembodiment.

FIG. 1B is a longitudinal view of a venous valve fabric skirt coveredframe according to an exemplary embodiment.

FIG. 1C is a longitudinal view of a venous valve leaflet attached toinflow tissue skirt according to an exemplary embodiment.

FIG. 1D is a side perspective of a venous valve with a fabric coveredframe, inflow skirt, and leaflet according to an exemplary embodiment.

FIG. 1E is a front cross-sectional perspective of a venous valve with afabric covered frame, inflow skirt, and leaflet according to anexemplary embodiment.

FIG. 2 is a side perspective of a venous valve frame according to anexemplary embodiment.

FIG. 3A is a 2-D flat view of a leaflet according to an exemplaryembodiment.

FIG. 3B is a 2-D flat view of a wall with leaflet and inflow skirt,where the monocusp is folded onto the wall and the inflow skirt isattached to the base of the leaflet according to an exemplaryembodiment.

FIG. 3C is a side perspective of a longitudinal view of a leaflet foldedonto the wall and attached to an inflow skirt to form a conduitaccording to an exemplary embodiment.

FIGS. 3D and 3E are an overview of parameters considered for a 10 mmtranscatheter venous valve and a representative monocusp belly curve inan exemplary embodiment.

FIG. 4A is a folded over leaflet where the smooth side is mostly tissueelastin fibers and the rough side is mostly tissue collagen fibers wherethe tissue composition is about 80% collagen, and about 20% elastin inexemplary embodiment.

FIG. 4B is the alignment of the suture holes on the folded leaflet cuspto those suture holes on the supporting wall in an exemplary embodiment.

FIG. 4C is the fixation of temporary stitches on commissures of thefolded leaflet in an exemplary embodiment.

FIG. 4D is a complete tissue leaflet sutured to supporting wall withoutan inflow skirt and supporting wall suturing, after the two temporarysutures at the corners have been removed in an exemplary embodiment.

FIG. 4E is a complete tissue leaflet sutured to supporting wall with aninflow skirt and temporary stitches securing inflow skirt to the leafletsupporting wall in an exemplary embodiment.

FIG. 4F is a complete tissue leaflet where the inflow skirt is in theprocess to be sutured from the tissue edge to margin of attachment in anexemplary embodiment.

FIG. 4G is a complete tissue leaflet where the inflow skirt is beingsutured and a triple lock knot following two-wrap blanket stitches issecuring the inflow skirt to the margin of attachment in exemplaryembodiment.

FIG. 4H is a complete tissue leaflet with the completed inflow skirtfully sutured to leaflet in an exemplary embodiment.

FIG. 4I is complete tissue leaflet with the completed inflow skirt fullysutured to leaflet, where the leaflet and skirt folded and sutured onends in the axial/longitudinal direction in anticipation for insertionand fixation in the frame in an exemplary embodiment.

FIG. 5 is a side perspective of a tissue skirt according to an exemplaryembodiment.

FIG. 6A is the covering for the frame wrapped around a mandrel in anexemplary embodiment.

FIG. 6B is the fabric skirt covering for the frame inserted into theframe using a mandrel in an exemplary embodiment.

FIG. 6C is the assembled the fabric covered frame subassembly in anexemplary embodiment.

FIG. 7 is a longitudinal perspective of a valve assembly where theperipheral sections and medial sections are identified to aid finalassembly in an exemplary embodiment.

FIG. 8A is a tissue leaflet subassembly on mandrel inserted into thecovered frame subassembly in an exemplary embodiment.

FIG. 8B is a tissue leaflet subassembly on mandrel inserted into thecovered frame subassembly where the first temporary stitch at one thecrown eyelets is mid-threading in an exemplary embodiment.

FIG. 9A is a view of the initial stitch for the transcatheter valvefinal assembly, where stitch is at the strut adjacent to bridge locatedat the peripheral side in an exemplary embodiment.

FIG. 9B is a top view of final assembly of the transcatheter valve wherethere is a formation of a single loop around a strut proximal to a strutbridge in an exemplary embodiment.

FIG. 9C is the transcatheter valve where there is re-entry of a curvedneedle with suture near the middle of the struts from tissue skirtinterior to exterior.

FIG. 9D is a view of final assembly of transcatheter valve where thereis a re-entry of curved needle with suture near the middle of strutsfrom tissue skirt interior to exterior in the exemplary embodiment.

FIG. 9E is a side view of a transcatheter valve assembly where thecurved needle is passed through the eyelet of crown with a suture in anexemplary embodiment.

FIG. 9F is a view of a knot being tied in a transcatheter valve assemblyin the eyelet in the crown in an exemplary embodiment.

FIG. 9G is a top view of a peripheral section of the transcatheter valveassembly where the curved needle is inserted with the suture through thefabric through the middle of diamond strut in an exemplary embodiment.

FIG. 9H is a top view of a peripheral section of the transcatheter valveassembly where the curved needle is exiting with the suture through thefabric exterior to form a loop around the strut in an exemplaryembodiment.

FIG. 9I is a top view of a peripheral section of the transcatheter valveassembly where the curved needle is exiting with the suture from thetissue skirt interior to exterior of fabric skirt to form a loop aroundthe bridge in an exemplary embodiment.

FIG. 9J is a above perspective of a final assembly of the transcathetervalve, where a loop is formed around a strut bridge with re-entry ofneedle and suture form exterior to interior of tissue skirt in anexemplary embodiment.

FIG. 10 is a side perspective of a disassembled delivery systemaccording to an exemplary embodiment.

FIG. 11A is a side cut-away perspective of an assembled delivery systemaccording to an exemplary embodiment.

FIG. 11B is a side cut-away perspective of a nose cone assembly withinner tube assembly and sheath assembly in the delivery device in anexemplary embodiment.

FIG. 12A is a longitudinal cut-away perspective of a crimping system(crimper) assembly according to an exemplary embodiment.

FIG. 12B is a loading of the transcatheter valve using a crimper andcrimper dowel onto the delivery system in an exemplary embodiment.

FIG. 12C is a side and slightly above perspective of a crimpercompressing a transcatheter valve, where a crimper dowel is used forassistance in an exemplary embodiment.

FIG. 12D is a side perspective of a crimper compressing a transcathetervalve, where a crimper dowel is used for assistance in an exemplaryembodiment.

FIG. 12E is an above view of a crimper compressing a transcathetervalve, where a crimper dowel is used for assistance in an exemplaryembodiment.

FIG. 12F is a longitudinal cut-away perspective of a crimping system(crimper) assembly according to an exemplary embodiment.

FIG. 12G is a side perspective of the crimping system (crimper) assemblyaccording to an exemplary embodiment shown in FIG. 12F.

DETAILED DESCRIPTION

FIGS. 1A, 1D, and 1E show the fabric covered frame assembly, wherein theframe 140, leaflet 130 and FIG. 1C 120, wall FIG. 1C 120, and inflowskirt FIG. 1C 110 have been fixed together. FIG. 1A is a longitudinalview of the assembled transcatheter valve, where the leaflet 130 iscomplete with a supporting wall FIG. 1C 120 and attached inflow skirtFIG. 1C 110 in a fabric covered frame assembly. In FIG. 1A, the ends 100of the frame are flared. The flared ends 100 can be between about 2 mmto about 10 mm from the beginning of the flare to the end of the flare.FIG. 1B is a longitudinal view of the fabric 105 covered frame assembly.

FIG. 1C is a longitudinal view of the assembled leaflet and inflow skirtprior to insertion to the covered frame in one embodiment. In FIG. 1C,the inflow skirt is identified as 110, where the continuous biologicleaflet is identified as 120. In 120 of FIG. 1C it shows one leafletthat has been formed from a flat sheet of the continuous biologicaltissue that is folded form a monocusp shape with a supporting wall. FIG.1D is a side perspective of the assembled transcatheter valve, where theleaflet is complete with a supporting wall and attached inflow skirt ina covered frame assembly. FIG. 1E is a front perspective of theassembled transcatheter valve, where the leaflet is complete with asupporting wall and attached inflow skirt in a covered frame assembly.

FIG. 2 is a venous valve frame without the covering in an exemplaryembodiment. FIG. 2 shows flared ends of the frame which are identifiedas 200. The eyelets in the crown of the frame are shown as 210 in FIG. 2. The bridges of the frame are shown at 220 in FIG. 2 . The struts ofthe frame are shown as 230 in FIG. 2 . In a preferred exemplaryembodiment, each section can comprise about twelve zigzag segments withabout twelve proximal peaks 240 and about twelve distal peaks 240. Thedesign of the frame provides radial strength and is compressible. Insome aspects, each section can comprise about four to sixteen proximalpeaks and about four to sixteen distal peaks.

In some aspects, the sections are interconnected by connecting everyalternating proximal peak of one section with alternating distal peak ofthe other section. In such aspects, there can be about six strut 230members between two sections. In some other aspects, the sections can beinterconnected by connecting every third alternating proximal peak ofone section with every third alternating distal peak of the othersection. In such aspects, there can be about four strut members betweentwo sections. In one aspect, the sections are rigidly interconnectedusing the strut members, which increases stability during valveplacement while balancing enough flexibility during valve function andrigidity in the vein. In one aspect, the geometry of interconnectionsformed by connecting every alternating proximal peak of one section withalternating distal peak of the other section provide enough flexibilityto accommodate and mimic the natural dilation and contraction of a vein,ensuring optimal stress distribution, and providing a proper fit acrossa broad range of vein sizes. In one aspect, the geometry of theinterconnections are designed with enough flexibility to accommodate andmimic the natural dilation and contraction caused by momentary increasesin pressure and/or blood flow, including increases caused by activity ofmuscles such as the calf muscle (e.g., during calf muscle contraction)and/or Valsalva maneuver.

FIG. 2 is an implantable frame that has suture holes 210 on one or bothends that can aid to attach the implantable frame to a valve assembly.In some specific aspects, the implantable frame has suture holes on bothends of the frame. In another embodiment, the suture holes 210 are atthe crowns 210 of the frame zigzags.

FIG. 3A is a cross-sectional view of an exemplary leaflet according toan exemplary embodiment of the present invention showing the leafletwithout an inflow skirt attached.

In one aspect of the exemplary embodiment, the leaflet's cusp is furtherformed by cutting the continuous biological tissue to a shape having atop section 320 resembling the shape of a cusp and a bottom section 310that is generally rectangular in shape; folding the top section 330 overthe bottom rectangular section such that the apex of the leaflet'smonocusp is created; and suturing the top section onto the bottomrectangular section of the biological tissue to form margins of themonocusp, which is FIG. 3B. The entire leaflet is FIG. 3A, where the topportion 320 is the cusp portion and 310 is the bottom portion, where 3is the belly curve before folded. The outline of the where the topsection 320 is folded is shown as 330.

FIG. 3B is a side perspective of the cross-sectional leaflet withsupporting wall 1 and inflow skirt 2, where the inflow skirt 2 isattached to the base of the leaflet in an exemplary embodiment. In oneaspect, an inflow skirt is attached to the wall, which provides a way toavoid flow disruption on the inflow side of the device. In a furtheraspect, the inflow skirt 2 is attached to the wall and leaflet 1. Insome specific aspects, the skirt 2 material can be made using abiological tissue from a xenogeneic source. The xenogeneic source can beselected from the group consisting of porcine, bovine, and equine. Inone aspect, the xenogeneic source is porcine. In another aspect, thexenogeneic source is a xenogeneic pericardium. In another aspect, thexenogeneic source is a porcine pericardium. In an aspect, the skirt 2material has a shape that is approximately rectangular.

FIG. 3C shows a side perspective of a folded leaflet 310 with skirt 2where suture holes 300 can be seen. The monocusp 320 is folded and theleaflet 310 with skirt 2 is folded. In one embodiment, the leaflet hasmultiple cusps, which could be bicuspid or tricuspid shape. In oneembodiment, the design of the leaflet includes a belly curve, describedfurther in connection with FIG. 3D.

FIG. 3D illustrates the various design shapes and angles in a leafletfor a transcatheter valve in accordance with an exemplary embodiment,including a preferred design that provides for beneficial operation ofthe valve and leaflet. For example, for a 10 mm transcatheter venousvalve, it can have a coaptation angle 340 of about 20-80 degrees, a freemargin angle 350 between commissure points of about 90-270 degrees, aleaflet total height 360 of about 6 mm-11 mm, an A+B to coaptationheight ratio of about 0.5-1, a commissure-to-commissure (CC)/flat width380 of about 12 mm-20 mm, a coaptation gap 390 of about 0-3 mm, and afree margin distance 370 of about 14 mm-27 mm, as shown in FIG. 3E.

FIG. 3E shows an alternative exemplary embodiment where the leaflet FIG.3A is formed for a 10 mm transcatheter venous valve having a preferreddesign that provides for beneficial operation of the valve and leafletaccording to an exemplary embodiment. For example, the leaflet designincludes various structural relationships such as belly curve having acoaptation angle of about 30-65 degrees, a free margin angle betweencommissure points of about 110-130 degrees, a leaflet total height ofabout 7 mm-10 mm, an A+B coaptation height ratio of about 0.85-0.95, acommissure-to-commissure (CC)/flat width of 16-18 mm, a coaptation gapof 0-2 mm, and a free margin distance of 17-22 mm.

A method for assembling a leaflet according to an exemplary embodimentof the present invention is illustrated in FIGS. 4A to 4I which showvarious stages of the leaflet 405 being formed. Inflow skirt 425 isfixed to the leaflet 405 in FIGS. 4E, 4G, 4H, and 4I. The inflow skirtcan be attached to the leaflet only on the in-flow side of the leafletto prevent wind socking issues. The inflow skirt material helps preventmigration and aids flow. The leaflet and inflow skirt may cover theentire valve in an exemplary embodiment.

In one exemplary embodiment, the at least one leaflet attached with theinflow skirt material when folded into a cylinder, has a diameter ofabout 6 to 12 mm. In one aspect, the at least one leaflet attached withthe inflow skirt material when folded into a cylinder has a diameter ofabout 9 mm to about 12 mm.

In accordance with another exemplary embodiment, the method comprisesproviding a continuous biological tissue subjected to a fixationtreatment; cutting the fixated biological tissue in a specific shape tohave a top section and a bottom section; folding the top section ontothe bottom such that an apex of a monocusp of a leaflet is created; andsuturing the top folded section onto the bottom folded section along themargins to form the monocusp shape of the leaflet. The method canfurther comprise attaching the monocusp leaflet onto a tissue inflowskirt with sutures. The method can further comprise attaching themonocusp leaflet sutured to the tissue inflow skirt onto a fabric skirt.

In one exemplary aspect, the suture holes onto the tissue are spacedabout 1.5 mm apart. In other aspects, suture holes can be spaced about0.5 mm to about 3 mm apart from one another. In another aspect, thesuturing spacing reduces leakage with overlap of sutures.

At the start of the leaflet manufacturing process, the at least oneleaflet can be formed from a flat sheet of the continuous biologicaltissue that is folded form a monocusp shape. In an exemplary embodiment,the exact geometry is not being replicated, but the function of thenative valve is achieved by causing the vortex operation with respect toblood flow using a monocusp leaflet that allows the leaflet to open andclose quickly. The leaflet's cusp can be folded from a continuousbiological tissue, and thus suturing is not required to form the apex ofthe leaflet's cusp. However, suturing can be used to form the margins ofthe leaflet's cusp. The leaflet in FIG. 4A is formed by laser cuttingPorcine Pericardial Tissue into a rectangular shape, where the animaldonors' cusp 415 remains intact.

In an exemplary embodiment, the smooth side of the leaflet,approximately a 10 mm, Porcine Pericardial Laser Cut Tissue, is formed.As shown in FIG. 4A, the smooth side can be elastin fiber and the roughside can be collagen, where the cross section is about 80% collagen, andabout 20% elastin. As seen in FIG. 4A, the leaflet is folded over asupporting wall, which shown in FIG. 4B is sourced from a xenogeneicsource, a porcine, in a laser cut rectangular shape with the smoothsides facing each other. The monocusp and the valve wall when the valveis in the open position, prevent or reduce adherence of the monocusp tothe valve wall and facilitating closing of the monocusp valve when flowpressure is reduced.

In FIG. 4B, suture holes formed in the supporting wall are aligned withthe folded leaflet cusp to those on the leaflet. Next, a sewing needlecan be taken with temporary sutures like PTFE and woven through thefirst matching holes at the upper left side to secure it in place. Theplaced temporary sutures can be seen in FIG. 4C at 400. The suturesshould be inserted into the suture holes and not into tissue surroundingthe suture holes. Excess sutures can be removed. These steps can berepeated in order to secure the wall and leaflet to each other whilemore permanent sutures are being placed. The temporary sutures 400reduce migration of the wall and leaflet and ensure the suture holesline up with the two pieces.

After the temporary sutures are in place, a sewing needle withpolybutester, monofilament, non-absorbable surgical suture can beinserted into the first matching holes of the upper left side of theleaflet and supporting wall. FIG. 4D shows a complete tissue leafletwithout a skirt and supporting wall suturing, after the two temporarysutures at the corners and the stitch of the cusp are completed. Byinserting the suture and needle into the same matching hole with thetemporary knot, the running stitch 410 can secure the wall to theleaflet. Excess sutures can be removed. In the next matching holes onthe same side of the leaflet, sewing can be continued to make a doublelock stitch. Once the last matching suture hole is reached, the needlecan be passed through to make a triple lock-stitch. This process can berepeated to stitch the other side 410 of the leaflet cusp. FIG. 4D showstwo temporary stitches at the corners of the leaflet commissures thatcan be removed using a suturing needle.

Afterwards, skirt 425 can be aligned to the inflow side of the leaflet405. The skirt and leaflet can be oriented such that the smooth side ofthe skirt 425 and supporting wall FIG. 4B are visible. Skirt 425 can befolded on top of the leaflet 405 such that the rough side of the skirtis visible. The bottom edge of the skirt 420 can be aligned with thebottom edge of the leaflet and supporting wall. The side edges of theskirt should also be aligned with the side edges of the supporting wall.For assembly of the leaflet assembly, a sewing needle with a temporarysuture like, PTFE, can be used. In an exemplary embodiment, the needleis inserted through the skirt 425 and out through the leaflet supportingwall and secure it, as shown in FIG. 4D at 410. The needle can beinserted approximately 1 mm from the lower edge of the tissue and 0.5 mmfrom the left edge of the tissue.

FIG. 4E shows temporary sutures 420 on the right and left sides ofleaflet and wall. Using, for example, a sewing needle with polybutester,monofilament, non-absorbable surgical suture and using the same suturehole as the temporary suture, the needle can be inserted through boththe tissue skirt 425 and leaflet 405 to secure the skirt to the leaflet.The temporary suture can then be removed so that the leaflet'ssupporting wall can be sutured to the skirt 425 along the bottom edgeusing, for example, a double lock-stitch. Suturing can continue up toapproximately 1 mm from the left side of the margin of attachment of thefolded cusp 415.

FIG. 4F illustrates sutures that can be spaced about 1 mm apart and 1 mmfrom the lower edge of the tissue 430. As shown in FIG. 4G, sutures canbe spaced about 1 mm apart and about 1 mm from the lower edge of thetissue.

FIG. 4H shows a skirt 435 that is unfolded from the leaflet, wall, andcusp 440 is folded along the axial direction so that the cusp is on theinterior of the fold. The edges of the tissue skirt/wall that willbecome the seam of the tissue subassembly can be aligned. Sutures can bespaced about 1 mm apart and about 1 mm from the lower edge of thetissue. As shown in FIG. 41 , the stitch can be located approximately0.5 mm from the outflow end of the tissue subassembly 445 and about 1 mmfrom the aligned edges of the subassembly.

FIG. 5 shows an unattached skirt. In one aspect, the skirt is attachedto the wall and leaflet skirt material. In some specific aspects, theskirt material can be made using a biological tissue from a xenogeneicsource. The xenogeneic source can be selected from the group consistingof porcine, bovine, and equine. In one aspect, the xenogeneic source isporcine. In another aspect, the xenogeneic source is a xenogeneicpericardium. In another aspect, the xenogeneic source is a porcinepericardium. In one aspect, the skirt material has the same source asthe monocusp leaflet. In some other aspects, the skirt material can bemade using a fabric. Such fabric can include PET, PTFE fabric, ePTFE,degradable scaffold, collagen scaffold, hyaluronic scaffold, fibrin, apolymer based degradable or non-degradable material, or a biologicmaterial. In one specific embodiment, the material has ultra-lowporosity, suture retention, surface roughness, scaffold of attachment,and surface area able to attract mesenchymal cells. In one aspect, theskirt is placed on the inflow side of the valve to help with flow.

The procedure for an exemplary embodiment of the covered frame assemblyis shown in FIGS. 6A, 6B, and 6C. A material for the covering for theframe assembly can include PET, PTFE fabric, ePTFE, degradable scaffold,collagen scaffold, hyaluronic scaffold, fibrin, a polymer baseddegradable or non-degradable material, or a biologic material. Thecovering for the frame is fixated to the frame. In an exemplaryembodiment, a polybutester suture is used as it is strong withmalleability.

FIGS. 6A, 6B, 6C shows the frame covering subassembly to be placed inthe frame. In an exemplary embodiment, to assemble the device a sewingneedle is prepared with polybutester, monofilament, non-absorbablesurgical suture. Then, the overlapping ends of the fabric skirt can begrabbed together (e.g., between the two longer ends) so that the ends ofthe fabric skirt come together and the fabric skirt can be wrappedaround the mandrel, identified as 620. The seam of fabric skirt can beparallel with the mandrel and the edge of the fabric skirt is extendedslightly past the end of the mandrel. Then the needle is inserted inwardapproximately 1 mm under the free edge located on the top of the skirt.The fixation should not be too close to the edge as the fabric couldtear, especially when using a suturing needle.

As shown, a knot can be made using the loose end loop, where the excessthread from the knot remains. Following that, the needle can bere-inserted into the same hole as to bring the needle to the outside,where a running stitch is made down the length of the overlap. As shownin FIG. 6A, the running stitch, identified as 600, can have about a 1 mmgap between each stitch. Once the stitches are at the bottom free edgeof the skirt, thread is wrapped around the end and the needle isinserted into the backside of the last stitch made. A running stitch inthe about 1 mm gaps can be created, leaving no more gaps in between eachstitch leaving the stitches to appear continuous. In FIG. 6A, thestitches reach the top free edge and an end knot is created.

Shown in FIG. 6B, the frame covering is loaded around a mandrel,identified as 620, through the inner diameter of the frame. Then to fixthe frame covering to the frame, a sewing needle is prepared with atemporary suture, such as PTFE. As shown in FIG. 6C, the overlap suturesare aligned on the frame covering with any eyelet in the crown,identified as 210 in FIG. 2, that corresponds and is in line to one ofthe frame's middle bridges. The eyelets in the crown of the frame areshown as 210 in FIG. 2 . The bridges of the frame are shown at 220 inFIG. 2 .

The outer diameter of the fabric skirt can be aligned with the eyeletsof the frame. From here, the frame covering (fabric skirt) can beattached to the frame by inserting the needle into any eyelet thatcorresponds to one of the frame middle bridges. To secure the framecovering, a knot with the loose end loop shown as 630 in FIG. 6C can beused. This process can be repeated using the same thread, for the nexteyelet, where a double lock stitch can be used by wrapping the loop ofthe previous suture around the needle twice. At the end of each suture,an end knot can be used and any excess thread can be trimmed for acompleted covered frame.

FIG. 7 shows the orientation and directionality for valve assemblypurposes in an exemplary embodiment. To assemble the tissue leaflet intothe previously created covered frame subassembly, the tissue leafletsubassembly can be placed and inserted over a tissue insertion mandrelhaving a diameter of about 9 mm, 9.5 mm, 10 mm, 10.5 mm, 11 mm, 11.5 mmor 12 mm, depending on the size of valve being assembled. Whileassembling, it is important to ensure the tissue leaflet subassembly iscentered on the mandrel and that the tissue is not damaged. Then, asseen in FIG. 8A, the tissue leaflet subassembly can be inserted on thetissue insertion mandrel 800 into the fabric skirt covered framesubassembly.

Once the tissue leaflet subassembly is inserted into the fabric skirtcovered frame assembly, the assembly will have inflow and outflowdirections by identifying the inflow end as the end where tissue inflowskirt is located and the outflow end as the opposite end. Followinginsertion of tissue, the mandrel 800 can be carefully removed, forexample using forceps to ensure that edge of tissue is flush withinflow/outflow diameters of frame and wrinkles are minimized.

FIG. 8A, shows an exemplary embodiment where the sewing needle and thetemporary suture, like PTFE, is used to sew into one of the frame'scrown eyelets 810 and are secured. FIG. 8B is the first temporary stitchat one of the crown eyelets 810; this step can be repeated for the fourother eyelets on each crown 805 of the valve assembly have a temporaryknot. The temporary knots should be placed equidistantly over the twelveeyelets of each crown (inflow/outflow) of the valve assembly. Adifferent number of eyelets can be used such as 6, 7, 8, 9, 10, 11 or12.

In FIG. 7 , the peripheral sections are shown as the flared ends of anexemplary embodiment. To attach the peripheral 915 section assembly usepolybutester, monofilament, non-absorbable surgical suture with a sewingneedle. As seen in FIG. 9A, begin suturing one of the peripheral 915sections (inflow or outflow). As suturing continues, locate a bridge 905connection and insert the needle near the bottom of the diamond strut925 on the peripheral section. As shown in FIG. 9A, the needle should beinserted on the outside of the diamond as shown in 900. FIG. 9B showsbringing the needle through the other side of the strut at 925 at 910.As shown in FIG. 9C, a prepared sewing needle with polybutester,monofilament, non-absorbable surgical suture, seen as 920, is insertedinto the first hole made. Next, the loop of the suture goes over theexcess thread, the loop is pulled and the excess thread can be trimmedoff

As shown in FIG. 9D, from the inner side of the frame, insert the needleon the side of the strut approximately 1 mm away from the previousstitch, approximately in the middle of the strut in an exemplaryembodiment. The sutures can be stitched around each strut 925 of theframe about three times. In another aspect, the sutures are stitchedaround each strut 925 of the frame from about one to about five times.The needle should go to the opposite side of the strut 925 that it wasinserted. On the outside of the frame, the needle can be inserted intothe outside of the diamond strut 925.

FIG. 9E shows that another stitch can be made around the diamond strut925 approximately 1 mm medial (away) from the last at the crown eyelet935. Then, the curved needle can be threaded through the eyelet 935 ofthe crown 935 and bring the suture out, as seen in FIG. 9E at 930. Asshown in FIG. 9F, a feather surgical blade can be used to remove thetemporary stitch before tying a double lock-stitch knot as shown in 940.In FIG. 9G, the needle can be reinserted through the middle of thediamond strut 925 at 945. In FIG. 9H, the re-inserted curved needle canbe threaded with sutures back through the interior of the tissue skirtand the needle is brought past the suture back out to the exterior andfrom the other side of the diamond strut 925. This is continued to matchthe suture pattern and configuration on both sides of the diamond strut925.

FIG. 9I shows an exemplary embodiment where the curved needled isre-inserted with suture back through the fabric skirt from the exteriorto the interior of the tissue skirt. Then the needle is brought out nearthe strut bridge at 950. If the strut 925 being sutured has a bridge 905connector to the adjacent section, an additional single loop stitch canbe created over the bridge 905 connector. As shown in FIG. 9J, thecurved needle with suture can be threaded over the bridge 905 and pastthe suture from exterior of fabric skirt to interior of tissue inflowskirt to form a loop around the bridge 905.

After suturing all frame 925 struts, an end knot can be created and theprior steps can be repeated for the other peripheral frame section usingpolybutester, monofilament, non-absorbable surgical suture and sewingneedle. The needle can be inserted immediately peripheral to the strutbridge 905 on one of the medial strut sections and secure the knot.Holding the leaflet open while suturing the medial sections of thetissue leaflet will help avoid damaging the leaflet. Since there are noeyelets for the medial sections, the single loop stitch should becontinued through medial struts. If the strut 925 being sutured has abridge 905 connector to the adjacent section, an additional single loopstitch over the bridge 905 connector can be created. These steps can berepeated for the remaining struts on the medial section 955. Aftersuturing all frame struts 925, an end knot can be created and repeatprior steps for the remaining medial frame section 955.

FIG. 10 shows a disassembled delivery system of where there is acapsule, catheter, pusher shaft, strain relief, lead screw, lead screwknob, handle shell (lower and upper), female connector, helical insert,BHCS, and loctite of one embodiment. In FIG. 10 , there is a handlesection, operational system, and catheter system has a housing area forthe valve. In FIG. 10 , the capsule or RO marker is identified as number1. This indicator is the point where the valve has passed; it must bedeployed and cannot be retracted back into the delivery device.

The capsule is identified as number 2. The catheter is identified asnumber 3; in one variation it is 0.159 in. The pusher shaft which helpsdeploy the valve is identified as number 4 in FIG. 10 . The pusher shaftis threaded through the catheter to aid loading of the valve. The tabholder is identified as number 5 in FIG. 10 . The strain relief isidentified as number 6 in FIG. 10 , where the lead screw is identifiedas number 7. The lead screw knob, identified as number 8 in FIG. 10 , iswhere an individual can turn the mechanism to retract the pusher shaftor extend the pusher shaft. These mechanisms above are covered partiallyby the handle shell, which is in two parts—lower, identified as 10, andupper, identified as 9 in FIG. 10 . The female connector is identifiedas 11 in FIG. 10 . The helical insert identified as 12 in FIG. 10 isinserted into the handle shell identified as 10 in FIG. 10 , where theBHCS is identified as 13 in FIG. 10 is inserted to the helical insert.The Loctite is identified as number 14 in FIG. 10 .

FIG. 11A shows the assembled delivery system in a split view. FIG. 11Bis a side cut-away perspective of a nose cone assembly with a sheathassembly that includes a nose cone as number 1 and a nose cone-braidedshaft as number 2, connected to the inner tube assembly's hypotube asnumber 3 in the delivery device in an exemplary embodiment system. Inthis embodiment, the three in one system allows for the device to notseparately need a dilator or introducer sheath, as the tapered bulletshape nose cone provides atraumatic entry acting as a dilator and thedistal region of catheter assembly has a continuous and uniform diameteracting as an introducer sheath.

FIG. 12A shows a crimper where 1 is the crimper front plate, 2 is thecrimper element, 3 is the crimper handle, 4 is the crimper base, 5 isthe crimper back plate, 6 is the spacer for screw, 7 is the crimperelement spring, and 8 is a socket head screw in an exemplary embodiment.The crimper is used to prepare the venous valve to be loaded into thedelivery system. As seen in FIG. 12B, the venous valve is placed in thecrimper and centered with the assistance of the crimper dowel 1205. Thecrimper dowel 1205 is used to assist the placement of the valve 1215 inthe crimper and guide it into the delivery device 1210 as seen in FIG.12B at 1200. FIG. 12C shows the crimper closed with the valve being heldin place and pushed into the delivery device to be loaded, where thedelivery device is shown as 1210. FIG. 12D shows another angle of acrimper, where the crimper dowel 1205 holds the delivery device inplace. FIG. 12E shows above angle of the crimper being used to load thedelivery device 1210.

Exemplary enumerated aspects of the present invention are set forthbelow.

1. A method of manufacturing a valve for transcatheter delivery anddeployment, comprising:

-   -   arranging a sheet of biological tissue in a substantially flat        orientation;    -   folding the sheet to form a monocusp shape having an apex and at        least two margins; and    -   forming a leaflet capable of placement via a catheter and        operating as a valve using the monocusp shape.        2. The method of example 1, further comprising suturing said        biological tissue to form the at least two margins of the        monocusp shape.        3. The method of example 1, wherein the biological tissue is        from a xenogeneic source.        4. The method of example 3, wherein the xenogeneic source is        selected from the group consisting of porcine, bovine, and        equine.        5. The method of example 4, wherein the xenogeneic source is        porcine.        6. The method of example 3, wherein the xenogeneic source is        pericardium.        7. The method of example 1, wherein the sheet is formed by        cutting a contiguous biological tissue to have a shape with a        top section and a bottom rectangular section.        8. The method of example 7, further comprising folding the top        section over the bottom rectangular section to create the apex        of the monocusp.        9. The method of example 8, further comprising suturing the top        section onto the bottom rectangular section to form margins of        the monocusp shape.        10. The method of example 10, wherein the leaflet is attached to        an inflow skirt material.        11. The method of example 10, wherein the inflow skirt material        is made using a biological tissue from a xenogeneic source.        12. The method of example 11, wherein the xenogeneic source is        selected from the group consisting of porcine, bovine, and        equine.        13. The method of example 11, wherein the xenogeneic source is        pericardium.        14. The method of example 10, wherein the inflow skirt material        is made using a non-biologic material.        15. The method of example 11, wherein the inflow skirt material        has a rectangular shape.        16. The method of example 11, wherein the inflow skirt material        has a generally rectangular shape with slightly wider end        sections.        17. The method of example 1, wherein the valve is attached to a        frame.        18. The method of example 17, wherein the leaflet is covered        with a fabric skirt before suturing it to the frame.        19. The method of example 10, wherein the leaflet attached to        the inflow skirt material is covered with a fabric skirt before        suturing it to a frame.        20. The method of example 1, wherein the valve is a cylinder        with a diameter of about 6 mm to about 18 mm.        21. The method of example 20, wherein the valve forms a        generally cylinder shape having a diameter of about 9 mm to 12        mm.        22. A method of manufacturing a replacement valve for        transcatheter delivery and deployment, comprising:    -   subjecting a continuous biological tissue to a fixation        treatment;    -   cutting the fixated biological tissue to have a top section and        a bottom section;    -   folding the top section onto the bottom section to form an apex        of a monocusp shape of a leaflet; and    -   attaching the top folded section onto the bottom folded section        to form a monocusp leaflet.        23. The method of example 22, further comprising attaching the        monocusp leaflet to an inflow tissue skirt with sutures.        24. The method of example 22, further comprising attaching the        monocusp leaflet onto a fabric skirt.        25. The method of example 22, wherein the biological tissue is        from a xenogeneic source.        26. The method of example 25, wherein the xenogeneic source is        selected from the group consisting of porcine, bovine, and        equine.        27. The method of example 26, wherein the xenogeneic source is        porcine.        28. The method of example 25, wherein the xenogeneic source is        pericardium.        29. A replacement valve, comprising:    -   a biological tissue subjected to a fixation treatment and cut to        have a top section and a bottom section;    -   an apex formed by folding the top section onto the bottom to        form the apex of a monocusp shape of a leaflet; and    -   a monocusp leaflet formed by attaching the top folded section        onto the bottom folded section, the leaflet providing a spatial        buffer between the monocusp and the valve wall when the valve is        in the open position, and facilitating closing of the monocusp        valve when adequate flow pressure gradient is created;    -   a frame coupled to the monocusp leaflet.        30. The valve of example 29, wherein the monocusp leaflet is        disposed towards one end of the frame.        31. The valve of example 29, wherein an inflow skirt is attached        to a valve wall to minimize disruption of flow and thrombosis.        32. The valve of example 29, wherein the monocusp leaflet is        folded from one continuous biological tissue without suturing to        form the apex of the monocusp leaflet.        33. The valve of example 32, wherein the monocusp has a belly        curve and at least one of a coalition angle of about 20 degrees        to 80 degrees, a free margin angle between commissure points of        about 90 degrees to 20 degrees, a leaflet total height of about        6 mm to 11 mm a coaptation height ratio of about 0.5-1, a        commissure-to-commissure (CC)/flat width of about 12 mm-20 mm, a        coaptation gap of about 0 to 3 mm, and a free margin distance of        about 14 mm-27 mm.        34. The valve of example 29, wherein the wall is attached to the        leaflet.        35. An implantable compressible vein frame, comprising:    -   a first section formed from a first plurality of segments;    -   a second section connected to the first section, the second        section formed from a second plurality of segments, wherein the        connected first section and second section form a hollow        cylinder; and    -   wherein the first plurality of segments includes a first        plurality of proximal peaks and a first plurality of distal        peaks and the second plurality of segments includes a second        plurality of proximal peaks and a second plurality of distal        peaks.        36. The vein frame of example 35, wherein each end of the        cylinder has a flare between about 0 mm to about 10 mm from the        beginning of the flare to the end of the flare and wherein the        hollow cylinder is compressible to 12 Fr-16 Fr.        37. The vein frame of example 35, wherein each end of the        cylinder has a flare that anchors or hooks the frame to the        natural tissue upon insertion.        38. The vein frame of example 35, further comprising a third        body section connected to the second section, the third section        formed from a third plurality of segments, wherein the connected        second section and third section form a hollow cylinder; and        wherein the second plurality of segments includes a third        plurality of proximal peaks and a second plurality of distal        peaks and the third plurality of segments includes a third        plurality of proximal peaks and a second plurality of distal        peaks.        39. The vein frame of example 38, further comprising a fourth        body section connected to the third section, the fourth section        formed from a fourth plurality of segments, wherein the        connected third section and fourth section form a hollow        cylinder; and wherein the third plurality of segments includes a        fourth plurality of proximal peaks and a third plurality of        distal peaks, and the fourth plurality of segments includes a        third plurality of proximal peaks and a second plurality of        distal peaks.        40. The vein frame of example 35, further comprising two to        sixteen crowns formed on each of the first section and the        second section to aid compressibility.        41. The vein frame of example 40, further comprising anchors or        hooks along the cylinder and at the crowns.        42. The vein frame of example 40, wherein a radial strength can        be 17-20 N, depending on the number of sections and crowns.        43. The vein frame of example 35, wherein the first section and        section are self-expanding or assisted with a balloon inflation        system.        44. The vein frame of example 35, wherein the first section and        second section are covered with a material including a fabric or        coating.        45. A method of manufacturing an implantable compressible vein        frame, comprising:    -   forming a first section from a first plurality of segments;    -   forming a second section connected to the first section, the        second section formed from a second plurality of segments,        wherein the connected first section and second section form a        hollow cylinder, each end of the cylinder being flared;    -   wherein the first plurality of segments includes a first        plurality of proximal peaks and a first plurality of distal        peaks, and the second plurality of segments includes a second        plurality of proximal peaks and a second plurality of distal        peaks providing stability and able to compress the structure;        46. The method of example 45, further comprising forming a third        body section connected to the second section, the third section        formed from a third plurality of segments, wherein the connected        second section and third section form a hollow cylinder; and        wherein the second plurality of segments includes a third        plurality of proximal peaks and a second plurality of distal        peaks, and the third plurality of segments includes a third        plurality of proximal peaks and a second plurality of distal        peaks.        47. The method of example 45, further comprising forming a        fourth body section connected to the third section, the fourth        section formed from a fourth plurality of segments, wherein the        connected third section and fourth section form a hollow        cylinder; and wherein the third plurality of segments includes a        fourth plurality of proximal peaks and a third plurality of        distal peaks and the fourth plurality of segments includes a        third plurality of proximal peaks and a second plurality of        distal peaks.        48. The method of example 45, further, comprising placing a        replacement valve leaflet within the first and second sections,        the replacement valve leaflet including a leaflet, a wall, and        an inflow skirt.        49. A crimping device, comprising:    -   a crimper front plate;    -   a crimper element coupled to the crimper front plate; and    -   a crimper handle coupled to the crimper element, wherein the        crimper element is adapted to receive a compressible vein frame        for transcatheter delivery of the frame into a vein.        50. The device of example 49, wherein the device compresses the        compressible vein frame into a cylindrical shape.        51. The device of example 49, further comprising a non-blood        contacting device with crimping dowel operable with the crimper        element, wherein the dowel is pushed through the crimper element        to guide the compressible vein frame while maintaining the        crimped state.        52. A delivery system, comprising: at least an inner tube        assembly; a sheath assembly coupled to the inner tube assembly;        a movable catheter assembly operable with the sheath assembly;        and a handle, wherein the catheter assembly is adapted to        receive a compressible vein frame for transcatheter delivery of        the frame into a vein.        53. The device of example 52 wherein the sheath assembly is        connected to the inner tube assembly by having the hypotube of        the inner tube assembly cover the nose cone-braided shaft of the        sheath assembly partially or completely, and wherein the sheath        assembly and inner tube assembly are capable of having a        standard guidewire pass through.        54. The device of example 53, wherein the catheter assembly is        slidably placed over the sheath assembly, and includes a        proximal region and a distal region.        55. The device of example 54, wherein one end of a proximal        region of the catheter assembly is connected to the handle and a        second end of the proximal region of the catheter assembly is        connected to the distal region of the catheter assembly, and        wherein the one end of the distal region of the catheter        assembly can be configured to compressively contain the        transcatheter valve in a compressed arrangement and the second        end of the distal region of the catheter assembly is connected        to the proximal region of the catheter assembly.        56. The device of example 55, wherein the handle is configured        to controllably move the catheter assembly relative to the        sheath assembly.        57. The device of example 55, wherein controllably moving the        handle provides a resting state in which a distal region of the        catheter assembly is closer to a nose cone or a delivery state        in which the distal region of the catheter assembly is pulled        away from a nose cone.        58. A crimping device, comprising:    -   a crimper front plate;    -   a crimper element coupled to the crimper front plate;    -   a crimper handle coupled to the crimper element, wherein the        crimper element is adapted to receive a compressible vein frame        for transcatheter delivery of the frame into a vein; and a        guiding dowel operable with the crimper element to assist        loading the crimper with a transcatheter device.        59. The device of example 58, wherein the guiding dowel has a        wider base to be gripped and narrows to thinly fit within the        crimping element.        60. The device of example 58, wherein the guiding dowel allows        for a nose cone of the transcatheter device to be threaded        through.        61. The device of example 60, wherein the guiding dowel is        pushed to guide the transcatheter device to be threaded while        maintaining the transcatheter in a crimped state.        62. A delivery system, comprising:    -   a first assembly including a catheter, a capsule, a handle top        and bottom shell, a pusher shaft, a tab holder, an indication        maker, a main screw knob, and a lead screw;    -   a second assembly coupled to the first assembly including a        delivery system flushing accessories and a nose cone assembly,        wherein there is a single diameter for the entire distal end of        first assembly and the distal end of second assembly.        63. The delivery system of example 62, wherein the first        assembly includes a tab holder at the end of a pusher shaft to        firmly hold the bottom of a device within the first assembly and        aid in releasing/deploying the device during implantation while        the pusher shaft maintains column strength.        64. The delivery system of example 63, wherein the pusher shaft        has a reduced diameter in a middle portion to prevent kinking        and to avoid friction during operation.        65. The delivery system of example 62, further comprising a        guiding dowel operable with the first assembly and the second        assembly to push a transcatheter device through a crimper to        guide the transcatheter device while maintaining the        transcatheter device in a crimped state.        66. The delivery system of example 62, wherein the nose cone        assembly and/or distal end of the catheter includes an        indication marker (radiopaque (RO) marker) that can be        visualized through fluoroscopy.

What is claimed is:
 1. A replacement valve, comprising: a biologicaltissue subjected to a fixation treatment and cut to have a top sectionand a bottom section; an apex formed by folding the top section onto thebottom to form the apex of a monocusp shape of a leaflet; and a monocuspleaflet formed by attaching the top folded section onto the bottomfolded section, the leaflet providing a spatial buffer between themonocusp and the valve wall when the valve is in the open position, andfacilitating closing of the monocusp valve when adequate flow pressuregradient is created; a frame coupled to the monocusp leaflet.
 2. Thevalve of claim 1, wherein the monocusp leaflet is disposed towards oneend of the frame.
 3. The valve of claim 1, wherein an inflow skirt isattached to a valve wall to minimize disruption of flow and thrombosis.4. The system of claim 1, wherein the monocusp leaflet is folded fromone continuous biological tissue without suturing to form the apex ofthe monocusp leaflet.
 5. The system of claim 4, wherein the monocusp hasa belly curve and at least one of a coalition angle of about 20 degreesto 80 degrees, a free margin angle between commissure points of about 90degrees to 20 degrees, a leaflet total height of about 6 mm to 11 mm acoaptation height ratio of about 0.5-1, a commissure-to-commissure(CC)/flat width of about 12 mm-20 mm, a coaptation gap of about 0 to 3mm, and a free margin distance of about 14 mm-27 mm.
 6. The system ofclaim 2, wherein the wall is attached to the leaflet.